Design, synthesis, and evaluation of JTE-013 derivatives as novel potent S1PR2 antagonists for recovering the sensitivity of colorectal cancer to 5-fluorouracil

Zhikun Guo,Shuai Zhang,Xiaochun Liu,Guangjian Zhao,Yingzhi Zhang,Dongdong Luo,Xuecui Zhao,Ximing Xu,Xianjun Qu,Lin Li,Shengbiao Wan,Shuxiang Cui

Bioorganic Chemistry（2023）

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摘要

•A series of S1PR2 antagonists were designed and synthesized to reverse 5-FU-resistance.•Compound 37 h could increase the intracellular 5-FU concentration by inhibiting the expression of DPD.•Compound 37 h showed a long half-life (t1/2 = 7.9 h) in SD rats.•Compound 37 h could effectively reverse 5-FU resistance in a SW620/5-FU mouse xenograft model.

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关键词

5-FU-resistance,S1PR2,DPD,Mouse xenograft model

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